tbuckley/cabot-search huggingface dataset:
A Controlled Trial of Methylprednisolone in the Emergency Treatment of Acute Asthma
Authors: Benjamin Littenberg, Eric H. Gluck
Journal: New England Journal of Medicine (1986)

Ninety-seven acutely ill patients with bronchial asthma were enrolled in a double-blind, placebo-controlled, randomized trial of intravenous methylprednisolone (125 mg), given on presentation in the emergency room in addition to standard emergency treatments for asthma. Subjective and spirometric indexes of the severity of the asthma were similar on entry into the study in all patients, but only 9 of 48 patients (19 percent) treated with methylprednisolone required hospital admission, as compared with 23 of 49 patients (47 percent) in the control group (P<0.003). Our results suggest that prompt use of glucocorticoids in the emergency treatment of severe asthma can prevent significant morbidity, reduce the number of hospitalizations, and effect substantial savings in health care costs. (N Engl J Med 1986; 314: 150–2.)
Hospital-Acquired Infections
Authors: Louis M. Sherwood, Edith E. Parris, Louis M. Sherwood, Edith E. Parris, David S. Feingold
Journal: New England Journal of Medicine (1970)

THE major infectious disease problems in most hospitals today are those that occur in the hospital — so-called nosocomial infections. In this discussion I shall define briefly the scope of the problem, explore some of the causes of the unacceptably high prevalence of hospital-acquired infections, evaluate some of the current preventive measures, and speculate on developments that may improve prevention and therapy. I shall focus on bacterial infections, although in certain classes of patients other organisms at times may be etiologic.The ProblemPrevalenceIn 1959, Rogers1 presented data from an autopsy study confirming that the types of infection causing . . .
Prostate Cancer in Transgender Women in the Veterans Affairs Health System, 2000-2022
Authors: Farnoosh Nik-Ahd, Amanda De Hoedt, Christi Butler, Jennifer T. Anger, Peter R. Carroll, Matthew R. Cooperberg, Stephen J. Freedland
Journal: JAMA (2023)

This case series investigates the rate of prostate cancer diagnoses among transgender women treated in the Veterans Affairs health system.
Reduction‐Responsive Supramolecular Sheets for Selective Regulation of Facultative Anaerobe Agglutination
Authors: Dawoon Lee, Longlong Dong, Ye Rim Kim, Jehan Kim, Myongsoo Lee, Yongju Kim
Journal: Advanced Healthcare Materials (2023)

Stimuli-responsive supramolecular materials have promising biological applications because of their ability to rapidly undergo significant structural changes in response to diverse stimuli. Herein, supramolecular sheets assembled via charge-transfer interactions between the pyrene moiety of a d-mannose-containing amphiphile and 7,7,8,8-tetracyanoquinodimethane (TCNQ) are reported. The supramolecular sheets show reduction-responsive behavior, in which their disassembly is triggered by the reduction of TCNQ by sodium sulfide. In an anaerobic environment, the sheet structure remains intact and the exposed d-mannose moieties induce the agglutination of facultative anaerobes, thereby inhibiting bacterial growth. In contrast, in an aerobic environment, the reduction of TCNQ by the hydrogen sulfide generated by facultative anaerobes causes sheet disassembly. This enables continuous bacterial growth, because the collapsed sheets cannot induce agglutination. Thus, this study presents a novel supramolecular material for the selective regulation of facultative anaerobe growth according to the external environment.
Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal
Authors: Carolina Pavlovsky, Bianca Vasconcelos Cordoba, María Belén Sanchez, Beatriz Moiraghi, Ana Varela, Rosario Custidiano, Isolda Fernandez, Maria Josefina Freitas, Maria Verónica Ventriglia, Georgina Bendek, Romina Mariano, María José Mela Osorio, Miguel Angel Pavlovsky, Ana García de Labanca, Cecilia Foncuberta, Isabel Giere, Masiel Vera, Mariana Juni, Jose Mordoh, Julio Cesar Sanchez Avalos, Gerardo Cueto, Silvia Miranda, Estrella Mariel Levy, Michele Bianchini
Journal: Journal of Hematology & Oncology (2023)

Abstract Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is safe under adequate molecular monitoring, but questions remain regarding which factors may be considered predictive for TFR. Argentina Stop Trial (AST) is a multicenter TFR trial showing that 65% of patients sustain molecular remission, and the prior time in deep molecular response (DMR) was associated with successful TFR. Luminex technology was used to characterize cytokines in plasma samples. Using machine learning algorithms, MCP-1 and IL-6 were identified as novel biomarkers and MCP-1 low /IL-6 low patients showed eightfold higher risk of relapse. These findings support the feasibility of TFR for patients in DMR and MCP-1/IL-6 plasma levels are strong predictive biomarkers.
Industry Payments to American Editorial Board Members of Major Urology Journals
Authors: David-Dan Nguyen, Liam Murad, Anne Xuan-Lan Nguyen, Anudari Zorigtbaatar, David Bouhadana, Claudia Deyirmendjian, Kevin C. Zorn, Dean Elterman, Bilal Chughtai, Rashid K. Sayyid, Muhieddine Labban, Quoc-Dien Trinh, Christopher J.D. Wallis, Naeem Bhojani
Journal: European Urology (2023)
Ultraviolet Light‐Based Micropattern Printing on Titanium Surfaces to Promote Early Osseointegration
Authors: Yiting Lou, Mouyuan Sun, Jingyu Zhang, Yu Wang, Haiying Ma, Zheyuan Sun, Shengjie Li, Xiaoyan Weng, Binbin Ying, Chao Liu, Mengfei Yu, Huiming Wang
Journal: Advanced Healthcare Materials (2023)

Patterned interfaces are widely used for surface modification of biomaterials because of a morphological unit similar to that of native tissue. However, engineering fast and cost-effective high-resolution micropatterns directly onto titanium surfaces remains a grand challenge. Herein, a simply designed ultraviolet (UV) light-based micropattern printing to obtain geometrical patterns on implant interfaces is fabricated by utilizing customized photomasks and titanium dioxide (TiO2 ) nanorods as a photo-responsive platform. The technique manipulates the cytoskeleton of micropatterning cells on the surface of TiO2 nanorods. The linear pattern surface shows the elongated morphology and parallel linear arrangements of human mesenchymal stem cells (hMSCs), significantly enhancing their osteogenic differentiation. In addition to the upregulated expression of key osteo-specific function genes in vitro, the accelerated osseointegration between the implant and the host bone is obtained in vivo. Further investigation indicates that the developed linear pattern surface has an outstanding effect on the cytoskeletal system, and finally activates Yes-Associated Protein (YAP)-mediated mechanotransduction pathways, initiating hMSCs osteogenic differentiation. This study not only offers a microfabrication method that can be extended to fabricate various shape- and size-controlled micropatterns on titanium surfaces, but also provides insight into the surface structure design for enhanced bone regeneration.
Copper Increases the Sensitivity of Cholangiocarcinoma Cells to Tripterine by Inhibiting TMX2‐Mediated Unfolded Protein Reaction Activation
Authors: Hongwen Liu, Lei Xu, Yiyang Zhang, Yiqiong Xie, Lishan Wang, Yue Zhou, Zhangding Wang, Yani Pan, Wenying Li, Lu Xu, Xinyun Xu, Ting Wang, Kui Meng, Jian He, Yudong Qiu, Guifang Xu, Weihong Ge, Yun Zhu, Lei Wang
Journal: Advanced Healthcare Materials (2023)

Chemotherapy-induced adaptive resistance is a significant factor that contributes to low therapeutic efficacy in tumor cells. The unfolded protein response (UPR) is a key mechanism in the development of drug resistance and serves as a critical reactive system for endoplasmic reticulum stress. Cu(II) can reduce the abundance of 60S ribosomal subunits and inhibit rRNA processing, leading to a decrease in the translation efficiency of the GRP78/BiP mRNA, which serves as a primary sensor for UPR activation. In this study, CuET-Lipid@Cela, composed of CuET and tripterine (Cela), demonstrates a significant synergistic antitumor effect on cholangiocarcinoma (CCA) cells. RNA-Seq is used to investigate the underlying mechanism, which suggests that the transmembrane protein 2 (TMX2) gene may be crucial in Cu(II) regulation of UPR by inhibiting the activation of GRP78/BiP and PERK/eIF2α. The synergistic antitumor efficacy of CuET-Lipid@Cela via inhibition of TMX2 is also confirmed in a myrAKT/YapS127A plasmid-induced primary CCA mouse model, providing new insights into the reversal of acquired chemotherapy-induced resistance in CCA.
Molecular mechanisms and therapeutic perspectives of peroxisome proliferator‐activated receptor α agonists in cardiovascular health and disease
Authors: Yujie Pu, Chak Kwong Cheng, Hongsong Zhang, Jiang‐Yun Luo, Li Wang, Brian Tomlinson, Yu Huang
Journal: Medicinal Research Reviews (2023)

The prevalence of cardiovascular disease (CVD) has been rising due to sedentary lifestyles and unhealthy dietary patterns. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor regulating multiple biological processes, such as lipid metabolism and inflammatory response critical to cardiovascular homeostasis. Healthy endothelial cells (ECs) lining the lumen of blood vessels maintains vascular homeostasis, where endothelial dysfunction associated with increased oxidative stress and inflammation triggers the pathogenesis of CVD. PPARα activation decreases endothelial inflammation and senescence, contributing to improved vascular function and reduced risk of atherosclerosis. Phenotypic switch and inflammation of vascular smooth muscle cells (VSMCs) exacerbate vascular dysfunction and atherogenesis, in which PPARα activation improves VSMC homeostasis. Different immune cells participate in the progression of vascular inflammation and atherosclerosis. PPARα in immune cells plays a critical role in immunological events, such as monocyte/macrophage adhesion and infiltration, macrophage polarization, dendritic cell (DC) embedment, T cell activation, and B cell differentiation. Cardiomyocyte dysfunction, a major risk factor for heart failure, can also be alleviated by PPARα activation through maintaining cardiac mitochondrial stability and inhibiting cardiac lipid accumulation, oxidative stress, inflammation, and fibrosis. This review discusses the current understanding and future perspectives on the role of PPARα in the regulation of the cardiovascular system as well as the clinical application of PPARα ligands.
Antiaggregation of NIR‐II Probe Regulated by Amphiphilic Polypeptide with High Contrast Brightness for Phototheranostics and Vascular Microscopic Imaging under 1064 nm Irradiation
Authors: Changchang Teng, Huiping Dang, Yixuan Xu, Dalong Yin, Lifeng Yan
Journal: Advanced Healthcare Materials (2023)

Thanks to deep penetration and high resolution, the second near-infrared window (NIR-II, 1000-1700 nm) fluorescence (FL) imaging is expected to gain favor in clinical applications, including macroscopic imaging for cancer diagnosis and microangiography for vascular-related disease diagnosis. Nevertheless, most NIR-II fluorescent probes, especially cyanine, are highly susceptible to self-quenching in the aggregated state, which severely limits their application in bioimaging. Here, the Br-modified cyanine dye F4 -Br and the amphiphilic polypeptide poly(oligo[ethylene glycol]methacrylate)-b-poly(benzyl-L-aspartic acid) (POEGMA-PBLA) are synthesized. By modulating the self-assembly of F4 -Br and POEGMA-PBLA to effectively inhibit the H-aggregation of F4 -Br in aqueous solutions, nanoprobe F4 -Br@P17 with outstanding antiquenching capability is developed. This prominent feature allows it to perform vascular microscopic imaging with high spatiotemporal resolution and assess hemodynamic characteristics. F4 -Br@P17 nanoparticles (NPs) with good stability and satisfactory biocompatibility also enable high contrast brightness for NIR-II FL imaging of tumors. Given the efficient enrichment at tumor sites and the promising photothermal conversion efficiency (43.5%), F4 -Br@P17 NPs successfully conduct photothermal therapy and exhibit superior antitumor efficiency under 1064 nm laser irradiation. These remarkable performances reveal the tremendous possibility of F4 -Br@P17 NPs for in vivo microscopic imaging and FL imaging-guided photothermal therapy in the NIR-II region.
Heavier Load Alters Upper Limb Muscle Synergy with Correlated fNIRS Responses in BA4 and BA6
Authors: Zhi Chen, Jin Yan, Xiaohui Song, Yongjun Qiao, Yong Joo Loh, Qing Xie, Chuanxin M. Niu
Journal: Cyborg and Bionic Systems (2023)

In neurorehabilitation, motor performances may improve if patients could accomplish the training by overcoming mechanical loads. When the load inertia is increased, it has been found to trigger linear responses in motor-related cortices. The cortical responses, however, are unclear whether they also correlate to changes in muscular patterns. Therefore, it remains difficult to justify the magnitude of load during rehabilitation because of the gap between cortical and muscular activation. Here, we test the hypothesis that increases in load inertia may alter the muscle synergies, and the change in synergy may correlate with cortical activation. Twelve healthy subjects participated in the study. Each subject lifted dumbbells (either 0, 3, or 15 pounds) from the resting position to the armpit repetitively at 1 Hz. Surface electromyographic signals were collected from 8 muscles around the shoulder and the elbow, and hemodynamic signals were collected using functional near-infrared spectroscopy from motor-related regions Brodmann Area 4 (BA4) and BA6. Results showed that, given higher inertia, the synergy vectors differed farther from the baseline. Moreover, synergy similarity on the vector decreased linearly with cortical responses in BA4 and BA6, which associated with increases in inertia. Despite studies in literature that movements with similar kinematics tend not to differ in synergy vectors, we show a different possibility that the synergy vectors may deviate from a baseline. At least 2 consequences of adding inertia have been identified: to decrease synergy similarity and to increase motor cortical activity. The dual effects potentially provide a new benchmark for therapeutic goal setting.
Atypical neurofibromatous lesions: Epigenetic cousins of other benign peripheral nerve sheath tumors?
Authors: Cristiane M Ida, Kenneth Aldape
Journal: Neuro-Oncology (2023)

Journal Article Atypical neurofibromatous lesions: Epigenetic cousins of other benign peripheral nerve sheath tumors? Get access Cristiane M Ida, Cristiane M Ida Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA Corresponding Author: Cristiane M. Ida, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA (Ida.Cristiane@mayo.edu). https://orcid.org/0000-0003-2768-2913 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth Aldape Kenneth Aldape Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA https://orcid.org/0000-0001-5119-7550 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 9, September 2023, Pages 1656–1657, https://doi.org/10.1093/neuonc/noad083 Published: 29 April 2023 Article history Published: 29 April 2023 Corrected and typeset: 11 May 2023
Profiling of small‐molecule necroptosis inhibitors based on the subpockets of kinase–ligand interactions
Authors: Lijuan Xu, Chunlin Zhuang
Journal: Medicinal Research Reviews (2023)

Abstract Necroptosis is a highly regulated cell death (RCD) form in various inflammatory diseases. Receptor‐interacting protein kinase 1 (RIPK1) and RIPK3 are involved in the pathway. Targeting the kinase domains of RIPK1 and/or 3 is a drug design strategy for related diseases. It is generally accepted that essential reoccurring features are observed across the human kinase domains, including RIPK1 and RIPK3. They present common N‐ and C‐terminal domains that are built up mostly by α‐helices and β‐sheets, respectively. The current RIPK1/3 kinase inhibitors mainly interact with the kinase catalytic cleft. This article aims to present an in‐depth profiling for ligand–kinase interactions in the crucial cleft areas by carefully aligning the kinase‐ligand cocrystal complexes or molecular docking models. The similarity and differential structural segments of ligands are systematically evaluated. New insights on the adaption of the conserved and selective kinase domains to the diversity of chemical scaffolds are also provided. In a word, our analysis can provide a better structural requirement for RIPK1 and RIPK3 inhibition and a guide for inhibitor discovery and optimization of their potency and selectivity.
Targeting epigenetic modifications in Parkinson's disease therapy
Authors: Dan Zhang, Jifa Zhang, Yuxi Wang, Guan Wang, Pan Tang, Yun Liu, Yiwen Zhang, Liang Ouyang
Journal: Medicinal Research Reviews (2023)

Abstract Parkinson's disease (PD) is a multifactorial disease due to a complex interplay between genetic and epigenetic factors. Recent efforts shed new light on the epigenetic mechanisms involved in regulating pathways related to the development of PD, including DNA methylation, posttranslational modifications of histones, and the presence of microRNA (miRNA or miR). Epigenetic regulators are potential therapeutic targets for neurodegenerative disorders. In the review, we aim to summarize mechanisms of epigenetic regulation in PD, and describe how the DNA methyltransferases, histone deacetylases, and histone acetyltransferases that mediate the key processes of PD are attractive therapeutic targets. We discuss the use of inhibitors and/or activators of these regulators in PD models or patients, and how these small molecule epigenetic modulators elicit neuroprotective effects. Further more, given the importance of miRNAs in PD, their contributions to the underlying mechanisms of PD will be discussed as well, together with miRNA‐based therapies.
A Mn Al double adjuvant nanovaccine to induce strong humoral and cellular immune responses
Authors: Nan Qiao, Hairui Wang, Yanhua Xu, Yu Chang, Mingxin Xie, Shuting Bai, Chunting He, Ming Qin, Xiaofang Zhong, Min Jiang, Zhaofei Guo, Guangsheng Du, Zhirong Zhang, Yuandong Zhang, Xun Sun
Journal: Journal of Controlled Release (2023)
Impact of Fibrinogen, Fibrin Thrombi, and Thrombin on Cancer Cell Extravasation Using In Vitro Microvascular Networks
Authors: Emmanouil Angelidakis, Sophia Chen, Shun Zhang, Zhengpeng Wan, Roger D. Kamm, Sarah E. Shelton
Journal: Advanced Healthcare Materials (2023)

Abstract A bidirectional association exists between metastatic dissemination and the hypercoagulable state associated with many types of cancer. As such, clinical studies have provided evidence that markers associated with elevated levels of coagulation and fibrinolysis correlate with decreased patient survival. However, elucidating the mechanisms underpinning the effects of different components of the coagulation system on metastasis formation is challenging both in animal models and 2D models lacking the complex cellular interactions necessary to model both thrombosis and metastasis. Here, an in vitro, 3D, microvascular model for observing the formation of fibrin thrombi is described, which is in turn used to study how different aspects of the hypercoagulable state associated with cancer affect the endothelium. Using this platform, cancer cells expressing ICAM‐1 are shown to form a fibrinogen‐dependent bridge and transmigrate through the endothelium more effectively. Cancer cells are also demonstrated to interact with fibrin thrombi, using them to adhere, spread, and enhance their extravasation efficiency. Finally, thrombin is also shown to enhance cancer cell extravasation. This system presents a physiologically relevant model of fibrin clot formation in the human microvasculature, enabling in‐depth investigation of the cellular interactions between cancer cells and the coagulation system affecting cancer cell extravasation.
Advanced models for respiratory disease and drug studies
Authors: Jesus Shrestha, Keshav Raj Paudel, Hojjatollah Nazari, Vivek Dharwal, Sajad Razavi Bazaz, Matt D. Johansen, Kamal Dua, Philip M. Hansbro, Majid Ebrahimi Warkiani
Journal: Medicinal Research Reviews (2023)

Abstract The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID‐19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung‐on‐a‐chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.
Circadian rhythm biomarker from wearable device data is related to concurrent antidepressant treatment response
Authors: Farzana Z. Ali, Ramin V. Parsey, Shan Lin, Joseph Schwartz, Christine DeLorenzo
Journal: npj Digital Medicine (2023)

Abstract Major depressive disorder (MDD) is associated with circadian rhythm disruption. Yet, no circadian rhythm biomarkers have been clinically validated for assessing antidepressant response. In this study, 40 participants with MDD provided actigraphy data using wearable devices for one week after initiating antidepressant treatment in a randomized, double-blind, placebo-controlled trial. Their depression severity was calculated pretreatment, after one week and eight weeks of treatment. This study assesses the relationship between parametric and nonparametric measures of circadian rhythm and change in depression. Results show significant association between a lower circadian quotient (reflecting less robust rhythmicity) and improvement in depression from baseline following first week of treatment (estimate = 0.11, F = 7.01, P = 0.01). There is insufficient evidence of an association between circadian rhythm measures acquired during the first week of treatment and outcomes after eight weeks of treatment. Despite this lack of association with future treatment outcome, this scalable, cost-effective biomarker may be useful for timely mental health care through remote monitoring of real-time changes in current depression.